This is an application for a "Mentored Patient-Oriented Research Career Development Award" (K23). My career objective is to be an independent investigator advancing the treatment of schizophrenia and related psychotic disorders, emphasizing early intervention strategies. This Award will provide me the research experiences, skills, and knowledge I need to develop and test novel treatment strategies, including early intervention in patients with schizophrenia and secondary prevention for patients at the prodromal stage of psychotic disorders. The career development plan includes: 1) mentored study of Biomedical Ethics, emphasizing exploration of ethical issues in the identification and treatment of prodromal symptoms; 2) tutorials aimed to facilitate the development of an independent research application. Readings, critical discussions, and the writing of summary conceptual papers and literature will focus on phenomenology and assessment of prodromal symptoms, "high risk" studies of schizophrenia, neurophysiological markers (e.g., p50 response) to identify "at risk" individuals, and intervention study design in first episode and prodromal stages of psychosis that will lead to conceptual and review papers; 3) advanced courses in biostatistics and epidemiology focusing on study design and data analytic methods appropriate to longitudinal studies and clinical trials; and 4) mentored conduct of clinical trials in first-episode schizophrenia and the prodromal stage of psychosis. The prodromal stage of psychotic illness has received little systematic study, yet the findings from first-episode studies that earlier intervention may improve prognosis have resulted in the initiation of clinical programs and treatment studies directed at prodromal symptoms. The lack of a well characterized prodromal state limits these efforts, especially since identifying individuals as "at risk" for a psychotic illness, and treating prodromal symptoms involve risks. The proposed research project will ascertain and prospectively follow 60 individuals with prodromal symptoms to determine risk of development of a DSM-IV psychotic illness. Refinements of the clinical criteria for prodromal state will be proposed based on the impact that specific clinical features, neurocognitive function, and family history of psychosis have on risk of development of psychosis. The study will also prospectively determine if stressful life events and substance use increase risk of progression to a psychotic disorder. The results of this study will guide the design of future intervention studies and are anticipated to provide pilot data for an R01 testing novel treatment strategies with patients in the prodromal stage of psychotic illness.